2-Decarboxy-2-tetrazolyl-19-hydroxy-19-methyl-6-oxo-PGF1 compounds

ABSTRACT

The present invention provides novel 2-decarboxy-2-tetrazolyl-19-hydroxy-19-methyl-6-oxo-PGF 1  compounds which are useful for pharmacological purposes, e.g., anti-asthmatic indications.

CROSS REFERENCE TO RELATED APPLICATION

The present invention is a divisional application of U.S. Ser. No.54,720, filed July 5, 1979, now U.S. Pat. No. 4,225,507.

BACKGROUND OF THE INVENTION

The present invention provides novel prostacyclin analogs. Particularly,the present invention relates to prostacyclin analogs substituted at theC-19 position by hydroxy.

Particularly, the present invention relates to2-decarboxy-2-tetrazolyl-19-hydroxy-19-methyl-6-oxo-PGF₁ compounds. Thenovel prostacyclin analogs are useful for pharmacological purposes,e.g., as anti-asthmatic agents. The preparation and use of thesecompounds is incorporated here by reference from U.S. Pat. No.4,225,507.

PRIOR ART

For background on prostacyclin, see for example R. A. Johnson, et al.,Prostaglandins 12, 915-928 (1976) and R. A. Johnson, et al., J. Am.Chem. Soc. 100, 7690-7704 (1978), and, as to pharmacological activity,the references cited therein. For analogs of prostacyclin, see, forexample, J. Fried, et al., Proc. Natl. Acad. Sci. U.S.A. 74, 2199-2203,K. C. Nicolaou, et al., J.C.S. Chem. Comm. 1977, 331-332, N. A. Nelson,J. Am. Chem. Soc. 99, 7362-7363 (1977), and K. Kojima, et al., Tetra.Letters, 1978, (1977), and K. Kojima, et al., Tetra. Letters, 1978,3743-3746. Regarding the nomenclature for analogs of PGI₂, see R. A.Johnson, et al., Prostaglandins 15, 737-740 (1978).

SUMMARY OF THE INVENTION

The present invention particularly provides a prostacyclin-type compoundof the formula ##STR1## wherein

D is --(CH₁)₂ --CO--CH₂ --L₂ -- or --CH₂ --CO--CH₂ --L₃ --

wherein L₂ is

(1) --(CH₂)_(j), wherein j is one to 4, inclusive,

(2) --(CH₂)_(q) --CF₂ --, wherein q is one, 2, or 3, or

(3) --CH═CH--,

wherein L₃ is

(1) --(CH₂)_(n) --, wherein n is one to 5, inclusive,

(2) --(CH₂)_(p) --CF₂ --, wherein p is 2, 3, or 4, or

(3) --CH₂ --CH═CH--;

wherein Q is oxo, α--H:βH, α--OH:β--R₄, or α--R₄ :β--OH,

wherein R₄ is hydrogen or alkyl of one to 4 carbon atoms, inclusive,

wherein R₂ is hydrogen, hydroxyl, or hydroxymethyl;

wherein R₅ and R₆ are hydrogen, alkyl of one to 4 carbon atoms,inclusive, or fluoro, being the same or different, with the proviso thatone of R₅ and R₆ is fluoro only when the other is hydrogen or fluoro;

wherein X is

(1) trans--CH═CH--,

(2) cis--CH═CH--,

(3) --C═C--, or

(4) --CH₂ CH₂ --.

I claim:
 1. A prostacyclin-type compound of the formula ##STR2## whereinD is --(CH₁)₂ --CO--CH₂ --L₂ -- or --CH₂ --CO--CH₂ --L₃ --wherein L₂ is(1) --(CH₂)_(j), wherein j is one to 4, inclusive, (2) --(CH₂)_(q) --CF₂--, wherein q is one, 2, or 3, or (3) --CH═CH--,wherein L₃ is (1)--(CH₂)_(n) --, wherein n is one to 5, inclusive, (2) --(CH₂)_(p) --CF₂--, wherein p is 2, 3, or 4, or (3) --CH₂ --CH═CH--;wherein Q is oxo,α--H:β--H, α--OH:β--R₄, or α--R₄ :--β--OH, wherein R₄ is hydrogen oralkyl of one to 4 carbon atoms, inclusive, wherein R₂ is hydrogen,hydroxyl, or hydroxymethyl; wherein R₅ and R₆ are hydrogen, alkyl of oneto 4 carbon atoms, inclusive, or fluoro, being the same or different,with the proviso that one of R₅ and R₆ is fluoro only when the other ishydrogen or fluoro; wherein X is(1) trans--CH═CH--, (2) cis--CH═CH--,(3) --C═C--, or (4) --CH₂ CH₂ --.